Matthew:
I think your nice summary leaves out an important point that has not been
explicitly mentioned. That is the question of whether depositing hydrogens
actually adds information to the model. I submit that for a typical protein
refinement it does not. The model is adequately described by saying
"hydrogens were added in their riding positions". This, together with
knowledge of the refinement program used, is sufficient to reconstruct
the full model.
This is an example of a recurring concern of mine that model validation
should include consideration of whether the model is overly complex.
Unless you have an abundance of data (which admittedly your 1.0Å case
might) there are insufficient observations to refine 3 positional parameters
for each hydrogen as if they were free variables. We typically bypass this
by instead using the riding hydrogen model, which adds effectively a single
on/off parameter for the entire mode (plus a small number of implicit
parameters that describe the ideal riding geometry, but those are
normally taken as a priori knowledge rather than free variables).
So I find deposition of hydrogens for a typical resolution structure to
be more misleading than useful. The correct, parsimonious, description is the
one-line statement that a riding hydrogen model was used.
It is tangential to your question, but I hold the same view about depositing
ANISOU records for a structure when the source of the anisotropy is solely
a TLS model, either with or without individual Biso contributions.
The parsimonious description is to give the TLS parameters and the Biso
component, if any. These can be expanded to regenerate per-atom
ANISOU parameters if desired by a downstream program.
If you deposit ANISOU records it implies that the Uij terms they describe
are free variables, but they are not. (or anyway IMHO they should not be,
although PHENIX can violate this stricture).
My view is that for a typical structure (i.e. worse than say 1Å resolution data)
depositing hydrogen positions and ANISOU records at best does no harm.
Unfortunately it implies a statistically unjustifiable model treatment.
The justifiable model is adequately described by the small number of
parameters in the header records; the hydrogen coordinates and ANISOU
parameters are redundant dross.
I fully understand that your original question was driven by cases where
you do have very high resolution data and so the statistical justification of
refining individual hydrogens or anisotropic ADPs enters a different realm.
Ethan
On Friday, 28 February 2020 20:22:17 PST Whitley, Matthew J wrote:
> Dear all,
>
> I want to thank everyone who responded to my query about whether or not to
> include hydrogens in PDB depositions when they were explicitly included in
> the model during refinement. In addition to the replies posted to this
> bulletin board, I received numerous replies sent directly to my email
> address.
>
> To clarify one more time for casual readers so that we are all on the same
> page: because these two structures happen to be at high resolution (1.0 and
> 1.2 Å, respectively), I decided to include explicit hydrogens in the model
> for refinement, as recommended by the documentation for both Phenix and
> Buster, which I used for these refinements. For the Phenix refinements,
> hydrogens were added by phenix.ready_set, whereas for the Buster
> refinements the hydrogenate tool was used. My understanding is that both
> of these eventually call the reduce tool from MolProbity. Unsurprisingly,
> the presence of hydrogens on the model led to both better model geometry
> and lower R-factors, although at these resolutions there is no observable
> density for the vast majority of the H-atoms in any of the refined maps.
>
> Because the presence of the hydrogens improved the model, I have decided to
> leave the hydrogens at their refined positions for deposition.
>
> I do want to point out one thing for readers interested in this topic: based
> on all the replies I received, there are a number of differing opinions
> (and therefore different practices) as to whether hydrogens should be
> included in deposited structures. The expressed opinions ranged from the
> ethical (if the hydrogens were there for refinement, then it’s only fair
> that they be present in the deposited structure so that downstream users
> know what went into generating the reported statistics) to the practical
> (if the paper’s conclusions don’t rely on any arguments based on hydrogen
> atom positions, then there’s no compelling reason for them to be there;
> include them or don’t, it doesn’t matter.) Because opinions seem to vary,
> perhaps it would be worthwhile for the PDB to issue some guidance on the
> matter for the future.
>
> Have a nice weekend, everyone.
>
> Matthew
>
> ---
> Matthew J. Whitley, Ph.D.
> Research Instructor
> Department of Pharmacology & Chemical Biology
> University of Pittsburgh School of Medicine
>
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